Thrombin generation following arterial injury is a critical initiating event in the pathogenesis of the proliferative stages of the atherosclerotic process
Research article published in Journal of vascular research (1994)
Abstract
Vascular injury, activation of the coagulation system and thrombosis are common initial events in the accelerated atherosclerotic process. The role of thrombin generated at the site of aortic injury in the subsequent neointimal proliferation was studied in rabbits (n = 16) 3 weeks after balloon catheter injury. In half of these animals, potent thrombin antagonists, r-hirudin and P-PACK, were administered to prevent acute thrombotic events. Compared to aortas with intact endothelium (n = 8), aortas de-endothelialised 21 days earlier showed neointimal hyperplasia as measured by the intimal/medial ratio (0.68 vs. 0.04, injured vs. normal aortas) and an increase in both total cholesterol (4.08 vs. 3.31 mg/g, p < 0.05) and lipid peroxide content (31.3 vs. 1.1 nmol/g; p < 0.001). Neointimal hyperplasia following endothelial denudation was inhibited in rabbits treated with thrombin-antagonists (0.27 vs. 0.68, treated vs. untreated, p = 0.012) and neither total cholesterol (3.48 mg/g) nor lipid peroxide content (1.5 nmol/g) differed significantly from that of intact arteries. By demonstrating a strong relationship between thrombin generation following de-endothelialisation and the progressive intimal proliferation, this study supports the hypothesis that thrombin is an important contributor to restenosis after vascular injury. The highly atherogenic lipid peroxidation seems to be linked to the early, thrombin-mediated events, as it was completely prevented by adequate thrombin antagonism.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Thrombin generation following arterial injury is a critical initiating event in the pathogenesis of the proliferative stages of the atherosclerotic process.
Por qué esto importa para la hirudoterapia
Este estudio examinó el papel de la generación de trombina en la proliferación neointimal y la aterogénesis tras una lesión aórtica con catéter-balón en conejos, administrando antagonistas de la trombina (r-hirudina y P-PACK) a la mitad de los animales para prevenir eventos trombóticos agudos. El tratamiento con antagonistas de la trombina inhibió significativamente la hiperplasia neointimal (cociente íntima/media 0,27 frente a 0,68, p = 0,012), y ni el colesterol total (3,48 mg/g) ni el contenido de peróxidos lipídicos (1,5 nmol/g) en las arterias tratadas difirieron significativamente de las arterias intactas. El resumen se refiere a 'r-hirudina' sin identificarla como derivada de sanguijuela; su conexión con la ASH o la hirudoterapia solo es inferible a partir de conocimiento general. El estudio es un modelo animal experimental de una molécula recombinante aislada, no un ensayo clínico ni una evaluación de hirudoterapia con organismos vivos.
Citación
Thrombin generation following arterial injury is a critical initiating event in the pathogenesis of the proliferative stages of the atherosclerotic process
Walters TK et al. · Journal of vascular research, 1994
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026